Naphazoline-induced Suppression of Aqueous Humor Pressure and Flow: Involvement of Central and Peripheral α2/I1Receptors

Abstract

The objective of this study was to examine the ocular hydrodynamic effects of topically and centrally administered naphazoline, alone and following pretreatment with pertussis toxin (PTX) and α2/I1receptor antagonists. Topically and intracisternally administered naphazoline was examined for its ability to alter intraocular pressure (IOP) of rabbits in the absence and presence of receptor antagonists (rauwolscine, efaroxan) and a Gi/oribosylating agent PTX. In addition, the topical effects of naphazoline on pupil diameter and aqueous humor flow rate were evaluated. Topical unilateral application of naphazoline (7.5, 25 and 75μ g; 25μ l) elicited an ipsilateral dose-dependent mydriasis (2, 4 and 5.5mm) that peaked at 2hr with a duration of up to 5hr. The IOP decreases induced by naphazoline were bilateral and dose-dependent (3, 6 and 10mmHg); the response peaked at 1hr and lasted for up to 5hr. Pretreatment with efaroxan (250μ g) elicited significantly greater antagonism of the ocular hypotensive response to naphazoline than did rauwolscine (250μ g) suggesting an involvement of imidazoline (I1) receptors. Intracisternal application of naphazoline (3.3μ g) also produced bilateral reductions (6mmHg) of IOP that were immediate (10min post drug) and lasted for approximately 2hr. In PTX-pretreated (2.5μ gkg−1, i.a.) rabbits, the ocular hypotensive effects of naphazoline by both routes (topically and centrally) were attenuated by 50–65%. In addition to producing ocular hypotension, topical application of naphazoline (75μ g; 25μ l) caused significant reduction, from 2.8 to 1.5μ lmin−1, in aqueous humor flow. These in vivo data indicate that, regardless of route of administration, alteration of aqueous humor flow by naphazoline was induced by the activation of α2and I1receptors. The ocular hypotensive effects produced by central administration did not result in sedation, therefore, there is the suggestion that central α2adrenergic receptors were stimulated minimally by naphazoline. Thus, these data suggest that ocular hypotensive effects and suppression of aqueous humor flow rate by naphazoline are mediated, in part, by α2and/or central I1at both central (brain) and peripheral (eye) sites. Moreover, these data indicate that the receptors are linked to PTX-sensitive G(i/o)proteins.